The synthetic peptides, DP107 and DP178, derived from gp41 ectodomain, have been shown to inhibit HIV-transition to a coiled-coil structure; suggesting that the corresponding region of gp41 undergoes structural rearrangement as an obligate step in membrane fusion. The second peptide, DP178 blocks HIV-1 mediated cell fusion at much lower concentration. The application focuses on the mechanism of action of DP178 by deriving virus "escape" mutants, and mapping the DP178 interactive sites. Correlations between the binding characteristics and the phenotypic changes of the escape mutants would support the critical role of these interactions in virus life cycle.